Vascular Extracellular Matrix Hydrogel

Abstract

Provided herein are methods of making an ECM gel from vascular tissue. Also provided herein are ECM compositions prepared from vascular tissue, and methods of use of those compositions, for example in treatment of aneurysms, and for vascularization or re-vascularization.

We claim: 
     
         1 . A method of preparing an extracellular matrix (ECM) material, comprising:
 a. incubating vascular adventitial tissue in a zwitterionic detergent;   b. incubating the tissue in an acid protease;   c. incubating the tissue with an anionic detergent;   d. disinfecting the tissue, thereby producing a decellularized ECM material;   e. lyophilizing the decellularized ECM material;   f. comminuting the decellularized ECM material;   g. at least partially solubilizing the decellularized ECM material with an acid protease, thereby producing solubilized ECM; and   h. neutralizing the solubilized ECM, thereby producing an ECM pre-gel.   
     
     
         2 . The method of  claim 1 , wherein the adventitial tissue is aortic adventitia. 
     
     
         3 . The method of  claim 1 , further comprising gelling the ECM pre-gel at a temperature at which the ECM pre-gel gels to produce an ECM gel. 
     
     
         4 . The method of  claim 1 , wherein the decellularized ECM material is not completely digested with the acid protease, thereby producing an ECM pre-gel comprising undigested decellularized ECM particles that gels at 37° C. 
     
     
         5 . The method of  claim 1 , further comprising at least one washing step prior to step e. 
     
     
         6 . The method of  claim 5 , wherein the at least one washing step comprises washing the tissue or material with phosphate-buffered saline, saline, and/or water. 
     
     
         7 . The method of  claim 1 , wherein the ECM material is prepared without a dialysis step or a crosslinking step. 
     
     
         8 . The method of  claim 1 , wherein the zwitterionic detergent is 3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate hydrate. 
     
     
         9 . The method of  claim 1 , wherein the anionic detergent is sodium dodecyl sulfate. 
     
     
         10 . The method of  claim 1 , wherein the acid protease is pepsin. 
     
     
         11 . The method of  claim 1 , wherein the decellularized ECM material is solubilized with an acid protease in a solution having a pH of from 1 to 4, from 1 to 2, or 2.0±0.3. 
     
     
         12 . The method of  claim 1 , further comprising dispersing the ECM in a natural or a synthetic polymer composition. 
     
     
         13 . The method of  claim 12 , wherein the natural or a synthetic polymer composition is one or more of: a second ECM material, fibrin, collagen, polyester (PE), polyurethane (PU), poly (ester urethane) urea (PEUU), poly (ether ester urethane) urea (PEEUU), poly (ester carbonate urethane) urea PECUU), poly (carbonate urethane) urea (PCUU) copolymer, polyolefin (polyalkene), polycarbonate, polyanhydride, polyether, polyurea, polyurethane, polyketone, and fluoropolymer. 
     
     
         14 . The method of  claim 12 , wherein the ECM is mixed with the natural or synthetic polymer composition prior to or during gelation of the ECM. 
     
     
         15 . The method of  claim 12 , wherein the ECM pre-gel is mixed with fibrin and fibrinogen and is gelled while the fibrin is cross-linked with the fibrinogen. 
     
     
         16 . The method of  claim 1 , wherein the vascular adventitial tissue is bovine, ovine, or porcine tissue. 
     
     
         17 . The method of  claim 1 , wherein step g. comprises completely solubilizing the decellularized ECM material with an acid protease. 
     
     
         18 . The method of  claim 1 , wherein the tissue is disinfected with peracetic acid. 
     
     
         19 . The method of  claim 1 , wherein the tissue consists essentially of vascular adventitial tissue. 
     
     
         20 . The method of  claim 1 , further comprising, before step a., isolating the vascular adventitial tissue by delaminating the adventitial layer from the medial layer of vascular tissue.